ENRADAS: Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on RAdiographic Damage in Ankylosing Spondylitis

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Completed

CT.gov ID

NCT00715091

Collaborator

(none)

180

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomised, controlled, multi-centre clinical trial on AS patients. Experimental intervention: continuous (daily) treatment with diclofenac cholestyramine 150 mg (Voltaren Resinate), divided into 75mg Voltaren twice dailyControl intervention: treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg (Voltaren Resinate). The treatment strategy of the control intervention (on-demand) reflects current clinical practice in AS. Duration of intervention per patient: 2 years Follow-up per patient: safety assessment 3 months after termination of the trial.

Condition or Disease	Intervention/Treatment	Phase
Ankylosing Spondylitis	Drug: diclophenac Drug: diclophenac	Phase 4

Detailed Description

Ankylosing spondylitis (AS) is a common chronic inflammatory rheumatic disease with a prevalence of about 0.5%. First symptoms normally occur in young adulthood. Early in its course, AS is dominated by chronic pain, fatigue and morning stiffness, later on by ankylosis and loss of function. Nonsteroidal anti-inflammatory drugs (NSAID) and tumor necrosis factor (TNF) alpha blocking agents are the only drugs with proven efficacy for signs and symptoms. It is not clear, however, whether these drugs are also capable of retarding or stopping structural damage, i.e. prevention of bony ankylosis. Earlier investigations indicated that NSAIDs have, in addition to their anti-inflammatory, also an anti-osteoproliferative effect. In this study we will investigate whether treatment with 150 mg diclofenac, a non-selective NSAID, on a daily basis (continuous treatment) over 2 years is capable to slow down the development of bony ankylosis as compared to treatment with 75-150mg diclofenac as needed according to clinical symptoms (on-demand treatment). In this national multi-centre randomized trial patients with symptomatic AS and indication for NSAID therapy will be enrolled in about 40 centres. The primary outcome parameter is the proportion of patients with radiographic progression in the spine after 2 years in each treatment arm. If continuous NSAID treatment results in less radiographic progression as compared to on-demand treatment, a true disease modifying effect of NSAID has to be assumed which will most likely change the place of NSAID treatment in AS.

Study Design

Study Type:

Interventional

Actual Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) - a Prospective Randomised Controlled Trial

Study Start Date :

Sep 1, 2008

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 continuous (daily) treatment with diclofenac cholestyramine 150 mg (Voltaren Resinate), divided into 75mg Voltaren twice daily	Drug: diclophenac continuous (daily) treatment of diclofenac cholestyramine 150 mg, divided into 75mg twice daily Other Names: voltaren resinat
Active Comparator: 2 treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg (Voltaren Resinate). The treatment strategy of the control intervention (on-demand) reflects current clinical practice in AS.	Drug: diclophenac treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg daily Other Names: Voltaren resinate

Arm

Intervention/Treatment

Experimental: 1

continuous (daily) treatment with diclofenac cholestyramine 150 mg (Voltaren Resinate), divided into 75mg Voltaren twice daily

Drug: diclophenac

continuous (daily) treatment of diclofenac cholestyramine 150 mg, divided into 75mg twice daily

Other Names:

voltaren resinat

Active Comparator: 2

treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg (Voltaren Resinate). The treatment strategy of the control intervention (on-demand) reflects current clinical practice in AS.

Drug: diclophenac

treatment on-demand (as needed) with diclofenac-cholestyramine 75 to 150 mg daily

Other Names:

Voltaren resinate

Outcome Measures

Primary Outcome Measures

radiographic change (mean) of the spine after 2 years in the per-protocol population. Radiographs will be collected and centrally digitized. Scoring will be done by 2 readers who were blinded to treatment and sequence of the films [2 years]

Secondary Outcome Measures

the proportions of patients with any progression (change in the mSASSS ≥ 1) and change in the mSASSS > smallest detectable change (SDC), i.e. change in mSASSS which is greater than the measurement error. [2 years]
ITT analysis of radiographic change. [2 years]
Change in VAS back pain, BASDAI, BASFI, BASMI, CRP. [2 years]
event rates of serious and non-serious adverse events will be documented and compared between the two groups. [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

AS according to mod. New York criteria
Patients must have radiographic damage (at least one syndesmophyte) of the spine but no complete ankylosis of the cervical and lumbar spine (these are patients at risk for further and more rapid radiographic progression)
Patients must have active disease at inclusion defined as BASDAI question 2 (related to back pain) >= 4 (VAS, range 0-10) without NSAID treatment and with a clinical indication for NSAID therapy based on signs and symptoms

Exclusion Criteria:

No radiographic damage (syndesmophyte) of the spine at baseline
Complete ankylosis of the cervical and lumbar spine
Inactive disease
Evidence of current or past peptic ulcer
Current or past coronary heart disease
Stroke or transient ischemic attack
Uncontrolled hypertension
Chronic renal failure (creatinine > 1.5mg/dl)
Impaired liver function
Pregnancy
Abnormal liver function (2x upper limit of normal)
Active hepatitis B or C, chronic or acute heart failure (NYHA III or IV) -
History of HIV infection
History of neoplastic disease (details please refer to exclusion criteria)
History of abuse of "hard" drugs or alcoholism
Concomitant treatment with steroids, TNF-blockers, other DMARDs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medizinische Universitätsklinik Innere Medizin	Tübingen	Baden-Württemberg	Germany	1072076
2	Praxis Dr. Jacki	Tübingen	Baden-Württemberg	Germany	72072
3	Praxis Dr. Manger	Bamberg	Bayern	Germany	96047
4	Praxis Dr. Ochs	Bayreuth	Bayern	Germany	95445
5	Praxis Dr. Kellner	München	Bayern	Germany	80639
6	Praxiszentrum St. Bonifazius	München	Bayern	Germany	81541
7	Gemeinschaftspraxis Dr. Göttl	Passau	Bayern	Germany	94032
8	Fachklinik Bad Bentheim	Bad Bentheim	Niedersachsen	Germany	48455
9	Praxis Dr. Rockwitz	Goslar	Niedersachsen	Germany	38640
10	Gemeinschaftspraxis Dr. von Hinüber	Hildesheim	Niedersachsen	Germany	31134
11	Gemeinschaftspraxis Dr. Gauler	Osnabrück	Niedersachsen	Germany	49076
12	Praxis Dr. Dockhorn	Weener	Niedersachsen	Germany	26828
13	Universitätsklinikum DüsseldorfKlink für Endokrinologie, Diabetologie und Rheumatologie	Düsseldorf	Nordrhein-Westfalen	Germany	40001
14	Rheumatologische Schwerpunktpraxis	Düsseldorf	Nordrhein-Westfalen	Germany	40217
15	Evangelisches Krankenhaus	Ratingen	Nordrhein-Westfalen	Germany	40882
16	Praxis Dr. Kramer	Remscheid	Nordrhein-Westfalen	Germany	42897
17	Praxis Dr. Schoo	Rheine	Nordrhein-Westfalen	Germany	48431
18	Rheumatologische Praxis Dr. Spieler	Zerbst	Sachsen-Anhalt	Germany	39261
19	Brandt	Berlin		Germany	12163
20	Praxis Mielke	Berlin		Germany	12627
21	Praxis Zinke	Berlin		Germany	13055
22	Gemeinschaftspraxis Dr. Schwenke	Dresden		Germany	01109
23	Praxis Dr. Pick	Grafschaft bei Bad Neuenahr-Ahrweiler		Germany	53501
24	Praxis Dr. Kühne	Haldensleben		Germany	39340
25	Rheumazentrum Ruhrgebiet, St. Josefs Krankenhaus	Herne		Germany	44652
26	St. Josefs-Krankenhaus, Rheumatologie	Herne		Germany	44652
27	Praxis Dr. Kapelle	Hoyerswerda		Germany	02977
28	Gemeinschaftspraxis Dr. Kolitsch	Katzhütte		Germany	98746
29	Praxis Dr. Gräßler	Pirna		Germany	01796
30	Praxis Bohl-Bühler	Potsdam		Germany	14469

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

Principal Investigator: Martin Rudwaleit, MD, Charité University, Berlin, Germany
Principal Investigator: Joachim Sieper, MD, Charité University, Berlin, Germany
Principal Investigator: Jürgen Braun, MD, Rheumazentrum Ruhrgebiet, Herne, Germany